The 220 KD isoform of CD45 recognized by the monoclonal antibody B220 is differentially expressed on lymphocyte subsets. Among B cells it appears to distinguish a subset of memory B cells as well as being expressed on non-isotype switched B cells that do not have a memory phenotype. Within the ALPS population, B220 is expressed on the characteristic alpha beta TcR double negative T cell. In addition, B220 positivity appears to herald lymphocyte apoptosis following lymphocyte activation. Finally, B220 expression is also noted on T cell large granular lymphocyte (LGL) leukemia. The expression of B220 represents a glycosylation modification of the CD45 molecule. These findings in the context of the specific clinical observations associated with B220 expression suggest that the control of CD45 glycosylation has a significant role in lymphcoyte homeostasis and trafficking. Current studies are being undertaken to further elucidate these issues.